This invention relates to a method for evaluating perinatal lung maturity.
Respiratory distress syndrome (RDS), which each year claims the lives of thousands of newborn, is a disease caused by a deficiency in pulmonary surfactant, a substance that reduces alveolar surface tension. The fetal lung produces surfactant that reaches the amniotic fluid; and it is known that at approximately 35 weeks gestation, the surfactant, predominantly dipalmitoyl lecithin, increases substantially. The relative or absolute quantity of this substance in amniotic fluid is conventionally used as a measure of lung maturity to evaluate the probability of survival after delivery.
Three laboratory tests for lecithin are presently in wide use: the ratio of lecithin (L) to sphingomyelin (S), often referred to as the L/S ratio; the bubble stability or shake test; and the determination of surface tension.
It has been confirmed experimentally, that an L/S ratio of two or more in amniotic fluid is indicative of lung maturity. If a fetus is delivered after this ratio is achieved, RDS generally does not occur. This test is well known and widely used, particularly when the fetus is to be delivered by Caesarian section and the degree of lung maturity must be established beforehand. In such case, a sample of amniotic fluid is taken, and within an hour or so, the L/S ratio can be determined. Reference (1) discusses 19 different techniques presently used for carrying out this test.
The bubble stability test, which is qualitative, is quicker and less complicated. It involves a shaking a mixture of amniotic fluid in ethanol to determine whether a stable foam is generated. The stability of the foam is considered to result from the presence of the surfactant since this lowers the surface tension of the fluid. This test is useful as a rapid screening procedure for fetal lung maturity because experience shows that a positive test is indicative of pulmonary maturity. Because of the high incidence of false negative results, however, a negative test is usually interpreted as indicating a more quantitative test must be carried out.
The lecithin concentration in amniotic fluid may be determined by various chemical processes or by chromatography apparatus. While this measurement should be superior to others that only indirectly measure lecithin, it is more time consuming by a factor of two or three as compared to determining the L/S ration, and technically is the most difficult.
A recent study, Reference (2), shows that the L/S ratio of tracheal and pharyngeal aspirates in newborns with severe RDS provides useful information in predicting the outcome of the disease. Based on this study, the prognosis is death within a relatively short time after birth for infants with clinical RDS whose L/S ratio is less than one. Thus, it is clear that the L/S ratio, and perhaps the bubble stability test and measurement of the lecithin concentration, are useful tools in evaluating perinatal lung maturity. Obviously, this is an area of great public interest and need, and considerable effort has been devoted to improving and to devising new techniques for this purpose.
It is therefore an object of this invention to provide a new and improved method that facilitates the evaluation of perinatal lung maturity by a faster and more accurate technique that is less complex than techniques heretofore known.